A life among the viruses

Jordi Casals-Ariet spent his life studying and categorizing viruses, and in 1969 his search for the agent behind the mysterious Lassa fever almost killed him. But his near-lethal infection paved the way for improvements in lab safety.

By Kendall Powell

When virologist Jordi Casals-Ariet, M.D., died last February at age 92, his obituaries highlighted two salient facets of his life; the system he designed for classifying the viruses that he spent his life studying, and how one of those viruses almost killed him in 1969.

The virus first appeared that same year in three missionary nurses in Nigeria—a mysterious fever killed two of them in days. Casals-Ariet’s laboratory at the School of Public Health seemed the logical place to study samples of the nurses’ blood containing the virus. The Yale Arbovirus Research Unit (YARU) held the world’s most extensive collection of arboviruses, which are spread by blood-sucking insects, and the presence of leading virologists on the faculty offered the best chance of isolating the agent behind the fever.

Casals-Ariet and Sonja M. Buckley, M.D., an expert in tissue cultures, took on the task of isolating and identifying the lethal virus, named Lassa for the Nigerian town where it appeared, and altered their laboratory methods accordingly. They limited access to the virus and sealed off several lab rooms at the Laboratory of Epidemiology and Public Health. “I slowed down and became meticulous in my techniques,” Buckley recalled in her autobiography, “since we could not know how highly virulent this infectious agent might be.”

Early in June 1969, three months after the virus arrived at Yale, Casals-Ariet fell ill with fever, chills and severe muscle aches, which he brushed off as a cold. By June 15 he was in an isolation unit. His only hope was the surviving nurse, Lily Pinneo, who was recovering at home in Rochester, N.Y. Researchers and doctors debated whether to give Casals her antibody-containing plasma. Although they were convinced he had Lassa fever, a confirmation would take 96 hours, time Casals didn’t have. If they were wrong, an infusion of antibodies might cause a cross-reaction. Robert W. McCollum, then chair of the Department of Epidemiology and Public Health, said YARU researchers ultimately recommended using the antibodies.

“Nobody knew what else to do,” he said in an interview from his home in New Hampshire.

Casals-Ariet recovered and continued his research. That Thanksgiving, however, lab technician Juan Roman became ill and died. Lassa fever was confirmed, sending chills through the research group—Roman had never worked with the virus. Work on the live virus was halted and all samples were sent to a maximum-security lab at the Centers for Disease Control (CDC).

How Casals-Ariet and Roman contracted Lassa fever remains a mystery. McCollum and others suspect that the two inhaled virus particles from dust kicked up by infected mice. Casals-Ariet worked in the same room with the cages and Roman may have passed by the room or talked to him from the doorway.

“The incident forced changes to biosafety nationally, and was one of the seminal events in [bringing about modern] biosafety,” said Ben Fontes, M.P.H., the biological safety officer for Yale and a Certified Biological Safety Professional accredited by the American Biological Safety Association. He credits the YARU group’s extremely careful precautions with preventing other infections at Yale. Yet, as a result of these and other laboratory infections, a classification system for viruses, bacteria and other pathogens was created to ensure safe working conditions. After Roman’s death, unidentified infectious agents like Lassa were sent to the safest possible lab facilities.

Casals-Ariet went on to investigate Lassa outbreaks in West Africa. In 1973 biologists in Sierra Leone, aided by the Yale and CDC teams, determined that Lassa virus spread from wild rats to humans. Casals-Ariet also worked with the CDC to set up what eventually became the World Health Organization’s reference collection of arboviruses. His longest-lasting research legacy, however, may be the virus classification system he developed that shows the relationships of different animal and human viruses—critical information for developing vaccines and tracking and treating epidemics.

His efforts to identify the virus underlying Lassa fever almost cost Jordi Casals-Ariet his life. It’s still unclear how, despite extraordinary laboratory precautions, he became infected.

Images

His efforts to identify the virus underlying Lassa fever almost cost Jordi Casals-Ariet his life. It’s still unclear how, despite extraordinary laboratory precautions, he became infected.

In June 1969, days before he became infected with Lassa fever, Casals-Ariet (second row, fifth from left) posed for an annual photo with the infectious disease faculty at the School of Public Health.

Sonja Buckley, an expert in tissue culture, collaborated with Casals-Ariet in the investigation of Lassa fever.